The objective of this research is to characterize the chemical and macromolecular structure and interactions of bronchial glycoproteins from normal human subjects and patients with chronic airways diseases such as chronic bronchitis and cystic fibrosis, so as to correlate structure with rheological properties of bronchial mucus. We will purify and fractionate glycoproteins and their subunits, remove the carbohydrate by beta-elimination, fractionate the oligosaccharides by size and charge, and determine their structures by methylation analysis and enzymatic degradation. We will degrade glycoprotein in step-wise fashion to generate trimmed and core glycoprotein. Monomeric glycoproteins, subunits, and derivatives will be analyzed by a variety of physical techniques, including quasielastic light scattering (QLS), sedimentation, transient electric bire-fringence, band electrophoresis, and viscometry, to determine their molecular weight, size, shape, charge, and hydration as functions of ionic strength pH and other solution conditions. The concentration dependence of sedimentation equilibrium, hydrodynamic, light scattering, and optical properties of glycoprotein solutions will be investigated to elucidate the thermodynamics, kinetics, and geometry of reversible and irreversible association and gelation, and their dependence on solvent composition. Comparisons will be made between glycoproteins of normal and diseased patients. We will use QLS as a noninvasive probe of the viscoelastic parameters of mucous and glycoprotein gels from normal and diseased patients, to establish correlations with glycoprotein composition, ionic effects, and mucolytic agents.